Intensive Control of Hypertension in Nephropathic Patients

In the AASK (African-American Study of Kidney Disease and Hypertension) trial, 1094 non-diabetic, black patients, with hypertension-related nephropathy, have been examined, randomizing them to a standard or intensive anti-hypertension treatment. In spite of the average pressure value obtained through intensive treatment (130/78 vs. 141/86 mmHg), the obtained composed outcome– a reduction of 50% in glomerular filtration, terminal-stage renal disease, death – has been reached with a similar frequency in the two groups. As to drugs, ramipril, metoprolole and amlodipine have been used: the best results have been obtained with the ACE-inhibitor. After the randomization phase, subjects have been followed for about 6 years in a phase of “cohort”, where the objective has been to reduce LHBP below 130/80 mmHg, treating everybody with ramipril (plus other drugs if necessary). During this phase, pressure has remained slightly lower in the group of the starting intensive treatment (about 3 mmHg lower) than in the group treated with the standard treatment. Now, the researchers of that trial have published the final data, at the end of 10 years of follow-up. The frequency of the composed endpoint (doubled creatinine, terminal renal failure, death) has remained similar in the two groups: about 7 events/100 people/year. But in subjects where, at the beginning of the trial, the proteins/creatinine relation went beyond 0.22 (corresponding more or less to 300 mg of proteinuria), the intensive control of pressure was associated with a significant decrease of the endpoint (Hazard Ratio 0.73). On the contrary, in subjects where the relation was ≤ 0.22 there have been no better results than the standard treatment.

In the overall, the AASK trial does not confirm the efficacy of an intensive treatment of hypertension in order to obtain an improvement in renal functions: only in patients with a renal compromising in progress, positive results can be obtained with an intensive pressure control, even if we do not know why.

Albuminuria, Glomerular Filtration and Mortality

The presence of albuminuria and the decrease of glomerular filtration (GFR) are indexes used to assess renal function, even if the values of normality levels are still debated. In order to clear up in a better way the problem and to verify also the influence of these parameters on mortality, a meta-analysis has been performed on 21 trials, involving about 1,200,000 patients: for over 100,000 of them it was possible to obtain the value of albumin/creatinine relation. Mortality risk was kept almost unchanging for GFR values between 75 and 105 ml/min/1.73 m2. HR (Hazard Ratio), instead, for mortality for any cause has been of 1.18, 1.57 and 3.14 for GFR values respectively of 60, 45 and 15 ml/min/1.73 m2. Examining the relation between the risk of overall morality and albumin/creatinine relation it was seen, instead, that, compared to a starting value of 5 mg/g, the increase in the relation at 10, 30 and 300 mg/g has implied a HR respectively of 1.20, 1.63 e 2.22. Albuminuria measurement through stick has given practically identical values compared to the ones obtained through the calculation of albumin/creatinine relation. Cardiovascular mortality reflects the overall one. The association between GFR and mortality was similar for all the considered values of albumin/creatinine and vice versa, that suggests there are independent risk factors for the two parameters, risk factors which have been completely independent from the other factors of cardiovascular risk.
The very wide trial confirms that albuminuria alone (a parameter which can be obtained easily and with low costs) represents an important parameter to be considered in the evaluation of the renal function impairment, with the same probability of other more sophisticated and complex parameters.

Beginning of Dialysis

We have recently seen a certain tendency to anticipate as much as possible the beginning of dialysis in patients with severe renal diseases, but is there an evidence justifying this tendency? In Australia and New Zealand a randomized trial has been performed, where 828 adults with chronic nephropathy have been assigned to dialysis according to the value of glomerular filtration, if it had decreased to 10-14 ml/min/m2 or 5-7 ml/min/m2. If the subjects randomized to the second group (late beginning) had presented symptoms justifying it, they would have been immediately sent to dialysis. During follow-up, averagely lasted 3.6 years, the overall mortality rate has been of 37% in both groups. The incidence of cardiovascular events, infections and complications of dialysis, too, have presented similar values and at the end of the trial it was seen that the values of glomerular filtrate, when dialysis was started, were different compared to what was expected, since many patients, assigned to a late beginning, in reality have started dialysis before the established time, because of the onset of alarming symptoms: filtrate values when dialysis started were 12.0 ml/min/m2 in the group of early beginning and 9.8 ml/min/m2 in the group of late beginning. In practice, the group of “delayed” beginning started dialysis with a time difference of about 6 months compared to the group of “early” beginning.

From the trial we can deduce that the level of glomerular filtrate at which dialysis can be started can be established in 5-7 ml/min/m2, since an early beginning implies no substantial benefits for nephropathic patients. The costs/benefits relation would take much advantage from this with no damage for patients.